A recent study published in eBioMedicine explored the clinical and laboratory predictors of mpox severity and duration. It also tested the correlation between viral load and disease severity in biological fluids.
Study: Clinical and laboratory predictors of mpox severity and duration: an Italian multicentre cohort study (mpox-Icona). Image Credit: QINQIE99/Shutterstock.com
Background
Since May 2022, several cases of mpox have been reported in more than 100 countries. Mpox has been classified as a sexually transmitted disease as its spread has been unprecedented, and novel clinical presentations and human-to-human transmission routes have been noted. Detection of viable mpox virus (MPXV) DNA was also done in seminal fluid.
Although complications have been noted, the disease typically heals spontaneously and lasts 2-4 weeks. Hospitalization rates have varied due to the policies and propensity to use this avenue as an isolation strategy.
The clinical severity and outcome of human mpox could be determined by several factors, such as prior vaccination or infection, viral clade, promptness of medical care, baseline health condition, and so on.
The factors affecting poor clinical outcomes and duration of disease should be studied to start treatment early and decide on the management type, i.e., at home or in a hospital.
In some patients, MPXV DNA has been detected after clinical recovery, despite the Centers for Disease Control and Prevention (CDC) guidelines to stop isolating once lesions have healed.
About the study
To shed further light on the risk factors associated with disease severity and duration, this study utilized data from an Italian multicentre historical cohort.
To characterize the kinetics of inflammatory markers and to understand virus detection in different compartments of the body post-clinical resolution, the risk factors associated with enhanced MPXV virulence were also studied.
The sample consisted of adults diagnosed with mpox between the months of May 2022 and September 2023. Follow-ups were conducted till clinical recovery. During the disease and post-recovery, biological fluid samples were collected from the patients.
The disease severity and its association with the cycle threshold value (Ct-value) formed the primary outcomes of interest. The Ct value acted as a proxy for viral load.
At the same time, the disease severity was gauged using data on the need for hospitalization, the presence of mucosal involvement, and the presence of an extended rash. Predictors of disease duration constituted the secondary outcomes.
Study findings
The sample comprised 541 patients, of which only four were women. The median age was 38 years and about 43% were people living with HIV (PLWH).
Approximately 4% of patients reported a CD4 count lower than 350 cells/ μL. No deaths were recorded but about 40% of patients experienced severe mpox. Eighty-one patients required hospitalization.
Concerning risk factors associated with severe disease, Caucasians and patients presenting with fever, sore throat, lymphadenopathy, and peri-anal lesions were more likely to experience severe mpox. Patients with penile localization were more likely to experience mild disease. No significant differences were noted by CD4 count or HIV status.
In a sub-group analysis involving 233 patients, a significant difference was noted between the median Ct-value for patients with either severe or mild infection.
This was done by assessing MPXV DNA in the upper respiratory tract in the first week of the disease. Accounting for heterogeneity across clinical centers, the likelihood of severe disease was noted to be inversely proportional to the Ct-value.
Also, a per unit increase in Ct-value led to a decrease in the risk of experiencing severe disease by 5%.
Multivariable analyses showed that patients with sore throat, proctitis, lymphadenopathy, and extended rash experienced more prolonged disease.
Furthermore, higher disease duration was noted among PLWH with a CD4 count lower than 350 cells/μL. Concerning temporal kinetics of inflammatory markers, C-reactive protein (CRP) and neutrophil-to-lymphocyte ratio (NLR) showed a robust log-linear association with time.
During the first week after symptom onset, the association was significantly above the upper standard limit. Over the next two weeks, the association normalized. No evidence of clinically significant organ injury was noted.
After clinical recovery, viral shedding was noted at several anatomical sites. This was confirmed by analyzing rectal swabs, seminal fluid, upper respiratory tract specimens, and urine specimens.
Conclusions
In sum, this study documented that mpox may last longer in cases of sore throat, proctitis, lymphadenopathy, and disseminated skin lesions. It may also last longer in PLWH with a low CD4 count.
Severe disease was more likely in Caucasian patients and those showing sore throat, fever, peri-anal lesions, and lymphadenopathy. No signs of organ damage were noted but viral shedding was noted at multiple anatomical sites after clinical recovery.
The data presented here may be useful for disease management and identifying patients who might experience severe disease.
New single-chain mRNA vaccines offer enhanced immunity and protection against mpox